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I wish I could help you, cat. All I know is from listening to docs I trust who work in ICU and in watching the hospitalization numbers, including numbers in ICU and deaths in my own area. In my area, younger people are indeed being hospitalized in greater numbers and some are critically ill and have been placed on a ventilator, though we know that’s usually the wrong choice. Deaths have ticked up steadily too over the last month to month and a half. Delta’s greater contagiousness, if that is true, could alone explain the increased hospitalizations since they seem to be getting much sicker much faster due to high viral loads perhaps. People were getting badly symptomatic on day 8-10 last year, now it’s moved down to day 4-5 where they are progressing to low oxygen levels. Kory and Marik corroborate that younger and younger people are being affected, likely due to those higher viral loads impacting them sooner. Anyway, as a retired ICU nurse and then an NP in internal medicine for a total of 34 years, something is definitely different with these variant, no question about it.

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the question is not "are cases up and are people getting nasty dose of covid?"

we know that.

they question is "why?"

people keep claiming it's the variant, but this does not seem to hold water esp on hosp and death rates.

i have a nasty suspicion that the vaccines are actually accelerating spread dramatically by allowing for very high VL, symptomatic carriers (who feel no symptoms BECAUSE they are vaccinated) that act like superspread bombs.

this is why i'd like to get to specifics on the variants and try to sort out what is what.

seems like a key piece of the puzzle, but i cannot quite find the shape of it.

but even if delta is an 11ish SAR vs an 8ish for alpha, cases are up WAY too much for it to be that alone.

something else is making them explode.

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I see what you are driving at. If you figure it out, I’m sure you’ll let us know. The next variant may be worse, however. Kory and Marik say Gamma has been a little monster down in South America. In any event, I’ve no doubt the vaccinated are spreading it with barely a symptom of their own at times. One anecdote does not constitute proof, but my 71 year old Pfizer vaxxed good friend got Covid from her 75 year old Moderna vaxxed husband… he had no symptoms to speak of at all. But she sure did. Fortunately, I saved her with liberal doses of ivermectin and even some fluvoxamine. Better in 4 days. Makes me want to avoid the vaccinated, frankly…

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Something else I thought about cat, is what Geert Vanden Bossche has been saying. He predicted younger and younger people will be affected in subsequent waves, mostly due to their sitting on suboptimal antibodies from a previous asymptomatic or barely symptomatic infection. He says it suppresses their innate immunity for a time, which is not spike specific but also less able to bind and neutralize the virus, neutralizing it, being the key to sequestration and control of the virus. That, coupled with the increased viral loads leading to quicker clotting and desaturation, could be the reasons.

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I do recommend you watch this interview of Vanden Bossche and Malone conducted by Philip McMillan of Vejon Health. It's long (~2 hours), but it make give insight. For example, Vanden Bossche has a theory as to why the case rate in the UK is hovering on a high plateau (also seen in Israel) that may play a role in the rising delta CFR.

https://www.facebook.com/162851011009411/videos/871272056853663

https://ourworldindata.org/coronavirus/country/united-kingdom

https://ourworldindata.org/coronavirus/country/israel

Thanks for all you do.

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i don't use facebook (and hate long form video as it's a very slow way to acquire data) any other way to get at this?

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founding

It appears to be on YouTube as well, so at least you can listen at a higher rate of speed than Facebook video allows. https://www.youtube.com/watch?v=qP31cfD3YOY

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Maybe it,s quicker to look up at Vanden Bossche's website FAQs

https://www.geertvandenbossche.org/faq

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It was a conversation about their theories...no data presentation.

Apparently, it's also on Youtube.

https://www.youtube.com/watch?v=qP31cfD3YOY

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Do you have the time stamp for the plateau theory portion?

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It starts around 34 minute mark. Vanden Bossche is trying to explain immune escape driven by the vaccinated. It's a rather long thread that concludes when the put up that case graph from Our World in Data.

Apparently, it's on YouTube as well:

https://www.youtube.com/watch?v=qP31cfD3YOY

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Here's a shorter one (11') with Weinstein:

https://youtu.be/WxlJcIea5VI

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Thank you!

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I think it's 22:00 - 33:00? That's where vanden Bossche discusses disablement of innate immunity leading to constant case plateau instead of waves; which is what I expected him to say since it matches his writing, but good to see that he is confident the Israel and UK data are supportive since I ventriloquized for him last week to that exact effect.

Thanks for the youtube link I was stuck in 1x on the FB.

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Yes. You're right. Thanks to WriterMomof4 for the YT heads up.

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Do you happen to have a link for a different way to watch the interview? I don't have a FB account. I see it's Vejon Health, but not sure if they published it somewhere else too. I hope so - I've never heard Bossche in an interview and would like to.

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Thank you for your work and your humility honesty.

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I think the reason that you are seeing delta looking like alpha now could be that to start with there is a substantial cohort who are more susceptible to it. They get sick first. They're done. Now we are only left with the more resistant people.

Isn't any nation doing random sampling of people with no symptoms to find out just how many of them are sick, unaware, and out there infecting others? I can't find any studies. I would think that this would be something everybody would be interested in knowing, so this puzzles me.

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"They get sick first. They're done. Now we are only left with the more resistant people."

That, combined with a downward slope for the population-wide "sterilizing" immunity that has dropped all summer long could account for the result (otherwise there should be a rise between April in June, followed by a steeper drop in July and August, if natural increase in infectious potency was working alone).

In the end the data can't possibly support Delta being more or less infectious than Alpha because Delta and Alpha aren't working with the same clay.

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That would be so smart. Therefore, it’s not happening. 🙄

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The problem with those numbers, as I understood them, was they were aggregates over all time and for all locations. But, over time and locations conditions change a lot making it hard to estimate transmission rate in general, and hard to compare because the data for different variants comes from different conditions. Among the potential confounders - lockdowns and vaccines are probably the biggest. I hadn't seen your figure 12 time series data, but a time series of estimates over bounded time intervals could allow better comparison of R0 estimates I think, without needing to control for so many variables. Of course to the extent that delta "took over" due to vaccine based selection, it's hard to get a handle that way on comparative R0.

I love how in this document they present this somewhat useless data (the aggregates) and then say, but you can't use these to compare variants because these aggregates are useless. Thanks, guys! Keep up the good work! (Grrrr! Hissss!)

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I've always been curious how SAR is measured. Wouldn't one expect SAR to drop over time due to rising seroprevalence?

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How did Delta crush the other variants if it is not more contagious?

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One possibility is that instead of modelling 'how contagious is the disease', which can have assumptions that the population is homogeneous in susceptibility, we should be modelling the susceptibility. It's instructive to look at 2020 figures for serious illness and death in South East Asia -- Vietnam, Japan, South Korea, China, Laos, Taiwan. Hardly any cases, and hardly any deaths. The countries that were seriously into masking and lockdowns claimed that this was the reason for their success, but other south-east Asian countries who didn't do much -- including Japan for most of 2020 -- also were also spared.

This looks like 'south-east Asians were resistant to covid in 2020' to me. So you then wonder -- is it their genes, or their environment, or prior contact with some other disease that gave them immunity? Somebody did a study in Thailand -- and unfortunately I cannot find it now -- which seemed to indicate that new immigrants (in the last 10 years) were much more likely to catch covid than those who immigrated from longer ago. They were looking for socio-and-economic factors related to poverty and income, but I said to myself 'looks like everybody got mildly sick with something more than 10 years ago, and it's protecting them now'.

Now we get to 2021. Along comes the delta variant. Cases spike in south-east Asia. Whatever was giving them resistance to catching earlier variants of covid does not work for delta, it seems.

I now wonder how much of the theory I learned in school 'over time, diseases mutate and become less lethal' is driven not by changes in the disease but in the susceptibility.

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Those are the countries where Sars 1 swept through?

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Depends on what you mean by 'swept through'. It is believed that Sars-1-cov was contained, because the people who caught pretty much all got very sick. Thus they were easy to quarantine, since they were in the hospital already. This would imply that sars-cov-1 never 'swept through' anywhere. However, should there be a mutation to sars-cov-1 which didn't make you ill, or very ill (I just had a runny nose for a few days) it is quite likely that it would spread unchecked. Because doctors weren't testing everybody with a runny nose for sars-cov-1 -- it was believed that you needed to be coughing to spread the disease, and this seems to be true or else a whole lot more people would have come down with the disease -- doctors could focus on testing those with severe symptoms.

But it sure doesn't seem to have made the people of Toronto immune to covid-2, consistent with the idea that sars-cov-1 was contained there.

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Understand that susceptibility is heterogeneous wrt geography and other factors. Not sure I get the significance for this question. What has changed is not susceptibility - it's the same populations. What has changed is the virus. It is more contagious.

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It's not 'the same populations' -- the populations change over time. Let us say that you have a new disease. 10% of the population is completely unprepared for this. They are going to get sick with it at the slightest exposure. 10% of the population had something very similar last year. You could sit them beside sick people all day long, give them the maximum exposure possible and they absolutely never will get sick. 80% of people are neither. So here we have a population where 90% are at risk for disease, and 10% are near certain to get it.

Let the disease go around infecting people for a while, until all of the 10% have become sick and recovered. (This is my imaginary disease, so I will make it one that doesn't kill anybody.)

Now when you look at the population, you see that the 10% that had something very similar last year still aren't getting sick. The 10% that were at great risk for infection, well they all got sick and now they are protected too from the illness they just had. They won't be getting it again. And those 80% in the middle? Most of them haven't been sick but some have. Let us say 5%. They are protected too.

Now we have a population where 75% are at risk. The virus is the same. The population has changed, by having members getting sick and becoming immune.

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That doesn't explain the increasing rate of infection. Subtracting the newly protected leaves a smaller pool. That should imply fewer infections, not more. That's why I claim that the changed virus is the reason.

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I think we are talking past each other. I think that the virus has changed, yes. What I am trying to understand is 'What does it mean when a virus variant where the secondary rate of infection is indistinguishable from a prior rate of infection is infecting a whole lot more people than the first variant'?

One possibility is that it is a whole lot milder, perhaps especially among the vaccinated. People get sick, and instead of feeling awful, and lying in bed at home and heading to the hospital, they are out and about their daily lives as if nothing has happened, because for them nothing very much has. You aren't more likely to catch alpha than delta, for the same amount of time of exposure to a sick person, you just are much more likely to meet a person with delta than with alpha. The alpha sufferers are all at home in bed.

But you could imagine a world where the delta variant was the first variant of the disease that started infecting people, and it went around the world until only those resistant to it were left uninfected. And then, randomly, the alpha variant shows up. Then what happens?

one possibility is -- nothing. The alpha variant doesn't spread at all. It is less successful than the delta variant, therefore any population in which delta isn't spreading (because the disease cannot find enough new people to infect) isn't going to spread the alpha variant either. This is the pattern for a disease that is about to die out, globally. No matter how the virus mutates, it still cannot get established again. The human immune system beats the virus here.

A different possibility is that the alpha takes off and starts infecting tons of people. This means that 'delta resistence' is different than 'alpha resistence'. If the people who are catching it also have milder symptoms, either because they have just taken a vaccine that is designed to prevent serious illness and death, or because the people who were for some reason more likely to get serious illness and death have already become sick, they will travel all around, infecting others and not staying in their bedrooms. Because, after all, they aren't feeling sick.

If the second is true, then whatever genetic changes the new variant has are less important in making people less sick than 'a close viral relative to me has been raging through here last year'. And we have no reason to be particularly hopeful that the whole disease will burn itself out. It could be like flu -- compared to the early days, almost nobody gets seriously ill and dies from it, but every year there is a new variant and some people will catch and spread it, and this continues forever. (Unless the people trying to develop a vaccine that will work on all flu variants are successful.)

I figure than both factors are

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"where the secondary rate of infection is indistinguishable from a prior rate of infection"

Where do you get that assertion?

If it is milder, why are the hospitals getting so many patients? Our treatment protocols are far advanced over last year. People go home sooner. And seniors are much better protected.

I've seen nothing that says that alpha and delta infect different people. Delta does not seem to escape the vaxes. But it has crushed alpha.

Almost every state has worse numbers than it did a year ago, despite the vax. That's amazing. It also says that winter is going to be nasty.

It's going to be like flu in that it isn't going anywhere. The difference is that if you have any health issues or you're old, delta is going to mess you up a lot worse. Flu has no mental issues and has no lasting outcomes (unless you die). Covid is different.

What I'm reading is that delta attacks faster, which means that our relatively slow testing and quarantine strategies are less likely to catch it before it spreads.

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ooops -- I figure that both factors are important. But I am beginning to doubt the meaningfulness of the 'infection rate' as a statistic. If you weren't and aren't doing random sampling of people who don't claim to be sick, then they are unmeasured. If there are hardly any of these asymptomatic spreaders, then this is fine. But if they are the majority than the picture that emerges from the data we get isn't the correct one.

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One thing that's never looked into is the microbiome. Most respiratory and gut viruses rely for cellular entry on some pathway that overlaps with microbiome bacterial metabolic and "immune" chemistry; thus, they only succeed if they are either passively or actively supported by these pathways.

Leaving aside the general importance of the gut microbiome in innate immune competence, which is more universal, there is a lot of regional variation in microbiotic motifs that could influence viral cellular entry fitness. Childhood diet regulates individual "default" microbiomes, with self-reinforcing effects for regionally dominant commensal strains. SARS-CoV-2 depends heavily on TMPRSS2, which is expressed everywhere but quite a bit in the mouth, to uncap the spike protein to allow for binding - has anyone looked into whether certain bacteria (or cigarette smoking, another regional distinction) makes TMPRSS2 less easy to access? Not as far as I know.

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Smoking increases TMPRSS2 expression but is not (probably not) a risk factor for severe covid according to https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014076/ (which refers to other articles).

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All true, but microbiomes haven't changed in the last 18 months. The virus has.

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Oh, I see by your above comment that I didn't really reply to what you are saying - that Delta (partially) conquered Asia because it is more contagious. However, that argument is circular - 'The reason Delta conquered Asia is because it is more contagious, and the proof that it is more contagious is because it conquered Asia.'

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I wasn't talking about Asia. I was talking about how Delta crushed the other variants and how I have no other explanation for that besides increased contagiousness.

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Right, I was replying more to Laura's musings than to your OP and should have realized sooner that your focus was on the OP.

RE that point, the latest video by JJ Couey litigates whether Delta's ascendancy over other variants is due to previous infection immunity escape pressure (Trevor Bedford's proposal) or vaccine immunity escape pressure (his view). I think it's the synthesis of both. https://www.twitch.tv/videos/1159285424?t=00h11m44s

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Which is neutral as far as "what is the _nature_ of the regional distinction that Delta solved." (On the other hand, it seems like east Asia has only been partially deciphered by Delta, given what a low fatality per cap Japan landed at after their summer wave; but this is also neutral.) However, I don't want to lean into the subject too heavily, I just think it's the default most plausible explanation absent any attempt to look into it.

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Per haps we are seeing a bit of what Liu et al. suggested may occur, https://www.biorxiv.org/content/10.1101/2021.08.22.457114v1 Delta is beginning to evade neutralizing immunity in vaccinated people but some enhancing effect remains, and CFR in vaxxed specifically is increasing?

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Yes, post-vaxed people are much more vulnerable to Delta than to Alpha. At least in the US, new cases are still mostly among the unvaxed.

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Since authors totally neglected to check whether the same "enhancement" occurs in their mutant versions of delta among non-vaccinated, infection-naive donor samples, the implications of that paper are provisional at best.

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The authors were asking a specific question. Non-vacc infection-naive people are a very small proportion of the population now, so would not significantly drive transmission.

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The specific question was highly tied up into their interrogation of the Covid-vaccine induced antibodies affinity for the N domain of the spike protein. If they had tested unvaccinated sera they could have ruled out any enhancement based on the vaccine-induced anti-N domain antibodies, suggesting they need to look somewhere totally different (such as something unique to their pseudo-virus vector, which naturally wouldn't apply to SARS-CoV-2 in the real world at all).

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Yeah agree. Would have made the argument stronger. Hopefully someone will.

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Or not... since it's essentially gain of function research in the first place.

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